This invention relates to a human intrauterine contraceptive device containing a contraceptionally active medicinal agent.
Contraceptives containing a medicinal agent for intrauterine application (IUD's) make available safely effective contraceptives without ovulation inhibition by using smaller quantities of active medicinal agent than are required when administered by way of the gastrointestinal tract. The human organism is accordingly burdened only with a minimum of medicinal agent and thus treated more gently; subjective as well as objective side effects are greatly reduced in comparison with other birth control techniques.
The use of IUD's widely differing with respect to material, configuration and effectiveness has been known for a long time. An early contraceptive means, to be used as an intrauterine device, was developed in 1920 by GRAEFENBERG with the utilization of a wire copper-silver alloy. The activity mechanism of presently known IUD contraceptive devices, however, has not yet been extensively clarified or fully understood.
Various synthetic resins, e.g. nylon, polyethylene, polyethylene/vinyl acetate, etc. have been employed in the pure form or with the addition of an X-ray contrast agent such as barium sulfate to obtain a great variety of IUD's. These devices, however, are relatively bulky and voluminous with respect to the typical dimensions of the uterine cavity, e.g. the MARGULIS coil of U.S. Pat. No. 3,200,815, German Patents 1,416,942 and 1,441,359; BIRNBERG's bow described in U.S. Pat. No. 3,253,590; the "Saf-T-Coil" of U.S. Pat. Nos. 3,234,938 and 3,374,788; and LIPPE's loop shown in U.S. Pat. No. 3,250,271.
All T-shaped devices have the common disadvantage that they cannot be sterilized in the applicator, due to the insufficient memory characteristic of the synthetic resin material. Insertion of the device into the applicator is hardly possible under aseptic conditions, since the device and the applicator are not adapted to each other in a suitable manner. Furthermore, the device and applicator together can lead to injuries during application, since the collapsed device and the upper rim of the insertion tube have sharp edges. The DALKON Shield and the applicator developed for this device are designed so that the insertion of the contraceptive is possible only with strong dilatation of the cervical canal.
The T-shaped contraceptive device of U.S. Pat. No. 3,533,406, the DALKON shield described in DOS (German Unexamined Laid-Open Application) 1,956,701 and LIPPE's LOOP D represent currently available intrauterine contraceptives made of a synthetic resin material which are smaller in circumference and volume than the aforementioned earlier devices. The reliability of these contraceptives can be enhanced by the application of metallic copper on the surface of the device; see Zipper, Amer. J. Obst. Gynec. 105, 1274-1278 (1969) and Jecht et al, Contraception 7 (5):381 (1973). Active medicinal agents such as pulverized copper or steroid hormones with a progestational gestagenic activity can be dispersed in the synthetic resin material. One kind of DALKON Shield, for example, contains copper distributed in highly dispersed form in the synthetic resin carrier. The COPPER-T and COPPER-7 devices of U.S. Pat. No. 3,563,235 are partially provided with a copper winding, while the COPPER TCu 220 C device of U.S. Pat. No. 3,533,406 is covered partially with copper sheaths.
The reliability of the contraceptive effect exhibited by intrauterine devices provided with copper on their surfaces can be further enhanced by the additional application of zinc or silver, see for example U.S. Pat. No. 3,563,235; Zipper et al., Amer. J. Obst. Gynec. 105:529-523 (1969a); and Zipper et al., Human Fertility Control Through the Use of Endouterine Metal Antagonism of Trace Elements in Control of Human Ferility, Nobel 15, Almquist & Wiksell, Stockholm (1971), page 199.
After application of intrauterine contraceptives containing medicinal agents, such as TCu 200 or TCu 220 C, of contraceptives containing copper and zinc, or of a device containing progesterone (German Pat. No. 2,247,949) or dl-11 .beta.-ethyl-17 .alpha.-ethinyl-17 .beta.-hydroxy-gon-4-3 n-3-one, reduced pregnancy rates are observed as compared to the intrauterine contraceptives which are manufactured solely of a synthetic resin material.
Intrauterine contraceptive devices consisting of a synthetic resin article and a silicone rubber capsule containing a medicinal agent connected thereto and are also known for use in the uterine cavity, e.g. see Int. J. Fert. 15:210 (1970). These medicine-containing IUD's however, just as the medicine-free devices of the same configuration, lead to undesired side effects such as bleeding and pain as has been reported by Fortier et al., J. Amer. Obst. Gynec. 115 (3):291-297 (1973); Tatum, Contraception 6 (3):179-189 (1972); Mishell et al., Amer. J. Obst. Gynec. 116 (8):1092-1096 (1973).
The most frequent side effects of conventional IUD's are hemorrhaging and pain. The number of intrauterinely applied contraceptive devices removed due to these complaints is greater in connection with the bulky synthetic resin devices than for the less bulky units, such as the DALKON Shield, T-shaped contraceptives, or LIPPE's LOOP D.
Side effects and removal necessitated by these side effects, as well as spontaneous expulsions of IUD's manufactured from a synthetic resin material are, however, due not only to unfavorable configurations and dimensions of these devices. Further essential factors in this connection are the elasticity and hardness of the synthetic resin material. Devices made of a plastic material too low in elasticity and too high in hardness often cause pains and cramps. Accordingly, these devices must be manufactured in various sizes, corresponding to the dimensions of the uterine cavity. Contraceptives made of a synthetic material that is too soft can jam by twisting in the uterus and are then often expelled spontaneously, or they can occasionally penetrate the uterus musculature. Fragments and intact devices of such IUD's, once having penetrated through the wall of the uterus, enter the abdominal cavity and can result in additional injuries such as strangled intestinal loops.
In general, less bulky intrauterine contraceptives made of a plastic material have been found to cause fewer side effects and spontaneous expulsions than bulky synthetic resin devices. The absolute number of undesired side effects and spontaneous expulsions is, however, still intolerable in both types for an intrauterine contraceptive. Even in the less bulky intrauterine contraceptives, one observes side effects such as the occurrence of dysmenorrhea, metromenorrhagias and leukorrhea associated with long-term pain and temporary cramp-like pain; see, for example, Ostergard et al., Contraception 4 (5):313-317 (1971); Portruff et al., Am. J. Obst. Gynec. 114 (7):934-937 (1972); Taylor et al., Obst. Gynec. 41 (3):404-413 (1973); Buchmann, Fert. Steril. 21 (4):348-355 (1970). The pregnancy rate, calculated according to the life-table method [Tietze, Intra-Uterine Contraception, Recommended Procedures for Data Analysis Studies in Family Planning, No. 18 (Suppl.), The Population Council, New York, 1967], is so high with the use of these contraceptives that the reliability of their effectiveness does not attain the reliability of conventional orally administered contraceptive hormones as reported by Fuchs et al., Contraception 5 (2):119-127 (1972); by Baeyertz, Austr. N. Z. J. Obst. Gynec. 11:117-121 (1971) and by Davis, Amer. J. Obst. Gynec. 114 (1):134-151 (1972). Buchmann, in Fert. Steril. 21 (4):384-355 (1973) has also reported that perforations of the uterine wall by this type of contraceptive device are frequently observed.
Rigidly shaped intrauterine contraceptive devices can break within the uterus when subjected to corresponding alternating bending stresses. The fragments can be expelled unnoticeably or, just as the intact devices, can penetrate the uterine wall and enter the abdominal cavity; see Last, J. Obst. Gynec. Brit. Commonw. 79 (2):190-191 (1972) and Domany et al., British Med. J. 1:549 (1973).
Disadvantages inherent in conventional IUD's include spontaneous expulsions, the occurrence of pregnancies, or the necessity for removing the device because of medical reasons. Removal of the IUD due to side effects is especially frequent at the beginning of the usage period, as reported by AVERY, Rep. Popul. Family Plan 4 (6):139 (1973).
In addition to the large number of necessary removals of these contraceptive articles due to medically intolerable side effects, spontaneous expulsions are reported by Fortier et al., Amer. J. Obst. Gynec. 115 (3):291-297 (1973); Johannisson, Contraception 8 (2):99-112 (1973); Snowden et al., Contraception 7 (2):91-104 (1973); and Horowitz, Contraception 7 (1):1-10 (1973). Spontaneous expulsions are observed with the DALKON Shield described in DOS (German Unexamined Laid-Open Application) 1,956,701 and Ostergard et al., Obst. Gynec. 41 (2):257-258 (1973), and with T-shaped contraceptives, e.g. copper-7; Newton et al., Lancet 1972/II No. 7784, 951-954; Bernstein et al., Contraception 6 (12):99-107 (1972), even though these devices are shaped with abutments arranged in opposition to the expulsion direction to avoid an ejection movement of the device, see Jones et al., Brit. Med. J. 3:143 (1973). In the DALKON Shield, these abutments are affixed to a ring in the form of laterial projections shaped like fingers and spikes. Intrauterine contraceptive devices shaped in this way inherently include the danger of uterus injuries not only during application, but during the period of use, see Koetsawang, Contraception 7 (4):327-332 (1973); Johannisson, Contraception 8 (2):99-112 (1973); Lehfeldt et al., Obst. Gynec. 37 (6):826-831 (1971); Brooks et al., Amer. J. Obst. Gynec. 113 (1):104-106 (1972); Sprague et al., Obst. Gynecol. 41 (1):80-82 (1973); Rienprayura et al., Contraception 7 (6):515-521 (1973), and also during removal, e.g. see Snowdon et al., Contraception 7 (2): 21-104 (1973). KAMAL et al., in Fert. Steril. 24 (3):165-169 (1973) state that minor injuries to the uterine wall, caused by the two horizontal ends of the T-shaped contraceptive of U.S. Pat. No. 3,533,406 which anchor the device within the uterine wall, are even advantageous for the effectiveness and fixation of the contraceptive device.
In the copper-containing IUD's such as COPPER-T, the copper wire under appropriate mechanical stress can break or can partially detach itself from the synthetic resin component. Such fragments of the copper wire can easily lead to injuries, as these fragments can penetrate the wall of the uterus and progress into the abdominal cavity and can be difficult to locate. In connection with the COPPER-TCu 220 C IUD, the danger of a uterine wall perforation with a subsequent separation of the copper cylinders and the danger that the copper cylinders remain in the abdominal cavity are especially great.
The heretofore customary IUD's are also disadvantageous with respect to their total weight and/or their weight distribution within the device, favoring a spontaneous expulsion. For example, the COPPER-TCu 220 C device weighs 612 mg. and one type of the LIPPES LOOP weighs 665 mg. Metal-containing IUD's such as that described in DOS 2,207,939, are readily spontaneously expelled due to the poor weight distribution within the device, with the metal rings are fixed in position exclusively at the shank of the synthetic resin component.
Other IUD's, for example in accordance with German Pat. No. 1,441,359 or DOS 2,207,939, have an extension of the coil to be applied by the intrauterine method, with the coil extension reaching from the uterine cavity through the cervical canal into the vagina. These devices are uniformly manufactured of a synthetic resin material. The synthetic resin best suited for the formation of the coil is, however, too rigid for the section located intracervically and intravaginally. Therefore, many side effects such as cramp-like pains and bleeding are observed for these IUD's which extend into the cervical canal; see WILLSON, Amer. J. Obst. Gynec. 92:62 (1965). A consequence of the uterine cramps is often unnoticed spontaneous expulsions and subsequent pregnancies.
Another disadvantage of conventional IUD's which contain medicinal agents is that the release of nonmetallic effective agents therefrom takes place, over the long-term duration, without the regularity required to maintain the contraceptive activity and without the dispensation of specific levels adjusted to predetermined limits. The manufacture of great numbers of these types of contraceptives is furthermore difficult from a technical viewpoint and can be accomplished only with the aid of a large number of different manufacturing steps.
The critical population problems of many countries have been magnified by the recent oil crisis. As it takes over a generation to achieve population stability once a zero population growth rate has been reached, there is an urgent need for contraceptive devices which are reliably effective without the aforementioned disadvantages of heretofore available IUD's. The present invention fills such needs.